DeGowin R L, Fisher P G, An D
J Lab Clin Med. 1987 Jun;109(6):679-86.
Eight daily intraperitoneal injections of endotoxin (LPS) induced hematologic abnormalities in mice like those previously observed with chronic inflammation, sterile abscess, and tumor bearing. By the ninth day, anemia, leukocytosis, hypocellularity of the bone marrow, and compensatory hemopoietic hyperplasia of the spleen had occurred. The suppressed hemopoietic recovery and impaired survival of mice with these abnormalities, after receiving an ordinarily sublethal dose of total body irradiation (600 cGy T.B.), confirmed their importance to the intact mouse and suggested that splenic hyperplasia was insufficient to compensate for a total body deficit of functional hemopoietic stem cells. Atrophy of hemopoietic tissue in the marrow with hyperplasia in the spleen implicated changes in the hemopoietic microenvironment to account for the different responses to endotoxin. Prostaglandin E2 (PGE2) serves as an important mediator of the inflammatory response and profoundly affects hemopoiesis. Previous studies had shown that low concentrations of PGE2 enhanced, and high concentrations suppressed erythropoiesis in vitro; therefore, we wondered whether stromal cells from the marrow's microenvironment produced more PGE2 in response to LPS than splenic stromal cells to explain the suppression of hemopoiesis in the marrow and its enhancement in the spleen. Indeed, synthesis of PGE2 in primary short-term cultures of adherent marrow stromal cells in response to LPS proved much greater than that observed in cultures of splenic stromal cells. Extending adherence times from 3 to 24 to 48 hours did not change the relationship. We believe that the results of our studies point to a role of PGE2 in the microenvironmental modulation of hemopoiesis in mice with activation of the inflammatory response.
每天腹腔注射内毒素（LPS）八天可诱导小鼠出现血液学异常，类似于先前在慢性炎症、无菌性脓肿和荷瘤小鼠中观察到的情况。到第九天，出现了贫血、白细胞增多、骨髓细胞减少以及脾脏代偿性造血增生。这些异常小鼠在接受通常亚致死剂量的全身照射（600 cGy全身照射）后，造血恢复受到抑制且存活率降低，这证实了这些异常对完整小鼠的重要性，并表明脾脏增生不足以弥补功能性造血干细胞的全身缺乏。骨髓造血组织萎缩而脾脏增生，这意味着造血微环境发生了变化，从而导致对内毒素的不同反应。前列腺素E2（PGE2）是炎症反应的重要介质，对造血有深远影响。先前的研究表明，低浓度的PGE2在体外可增强红细胞生成，而高浓度则抑制红细胞生成；因此，我们想知道骨髓微环境中的基质细胞对LPS产生的PGE2是否比脾基质细胞更多，以解释骨髓造血抑制和脾脏造血增强的现象。事实上，贴壁骨髓基质细胞原代短期培养物中对LPS反应的PGE2合成量远大于脾基质细胞培养物中的合成量。将贴壁时间从3小时延长至24小时再到48小时，这种关系并未改变。我们认为，我们的研究结果表明PGE2在炎症反应激活的小鼠造血微环境调节中发挥作用。
